This application requests funds to purchase an Abberior FACILITY LINE easy3D-STED fluorescence microscope to be included in the existing Integrated Cellular Imaging Core (ICIC). The primary goal of the ICIC is to provide investigators at Emory and surrounding Georgia institutions access to cutting edge light-based microscope technology, services, and expertise. This open shared resource has assisted 175 NIH grants held by 192 investigators in the last 2 FYs. Within the facility, the Abberior STED microscope will be used to study diverse aspects of molecular level organization pertaining to health and disease that include: axonal regeneration (Alvarez), muscle sarcomere function (Benian), mitochondrial regulation (Kahn), epithelial barrier function (Koval), cell junctions (Kowalczyk), viral genomic fitness (Lowen), viral entry and uncoating (Melikian), antiviral development (Sarafianos), MSC-induced immune regulation (Horwitz), retinal pigment epithelium (Nickerson) and mitochondrial membrane potential (Kenney). The Abberior easy3D-STED combines a unique balance of real-time super-resolution, ease of use, flexibility, and speed, thus providing researchers with expedited answers to their disease related molecular level questions. Adjustable real-time 3D super-resolution incorporated into a familiar laser scanning confocal microscope makes this system one of the most approachable super-resolution microscopes. Flexible ultra-sensitive photon- counting four-spectral-channel detection provides a sustained application across a busy core facility within an evolving experimental landscape. This resolution, ease of use, and sensitivity coupled with adaptive illumination controlled and drift-compensated STED makes 4-color real-time live-cell 3D imaging at the nanoscale now possible, providing huge impact for the research community in an almost unlimited number of investigations. This microscope will be managed as part of the facilities under the same stringent policies to ensure optimal usage and minimize downtime. Our facility has a strong financial commitment from the School of Medicine and Winship Cancer Institute, including deficit coverage, seed funding, and pilot grants. We feel the Abberior STED is an essential tool for addressing both current and future research needs of a largely NIH funded research community at Emory and surrounding institutions.